Low Dose Azacitidine after Transplant in Preventing Recurrence in Patients with Myelodysplastic Syndromes or Acute Myeloid Leukemia in Remission
- Patients who have undergone T-cell depleted allogeneic hematopoietic stem cell transplantation at Memorial Sloan-Kettering Cancer Center (MSKCC) for:
- De novo myelodysplastic syndromes (MDS): International Prognostic Scoring System intermediate-1 (IPSS-1) with poor risk cytogenetics or higher IPSS
- Acute myelogenous leukemia (AML) in first remission that required more than 1 cycle of treatment to achieve remission or with the following cytogenetic abnormalities: FLT3 mutation, deletion/monosomy of chromosome 5 or 7, MLL gene rearrangement, or more than or equal to 3 cytogenetics abnormalities; also patients in second or greater remission
- Patients with secondary MDS/AML
- Patients will be considered eligible for the study if after transplant they achieved hematologic (< 5% blasts) and cytogenetic remission
- Patients will be eligible to enter the study between 60-120 days post-transplant
- Karnofsky performance status >= 60% for patients > 16 years old (yo) and Lansky performance status >= 60% for patients =< 16 yo
- Absolute neutrophil count (ANC) > 1000/uL not supported by transfusions
- Hemoglobin (Hb) > 8 gr/dL not supported by transfusions
- Platelets > 50,000/uL not supported by transfusions
- Serum creatinine < 1.5 upper limit of normal (ULN)
- < 3 x ULN alanine aminotransferase (ALT), unless there is congenital benign hyperbilirubinemia
- < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia
- Adequate cardiac function measured by left ventricular ejection fraction (LVEF) > 50%; if asymptomatic, pre-transplant echocardiogram is adequate; if symptomatic, echocardiogram needs to be repeated
- Each patient must be willing to participate as a research subject and must sign an informed consent form
- Patients who were treated with 5'-azacitidine without response prior to transplant would be eligible to participate on this protocol
- Active uncontrolled bacteria, fungal or viral infection
- Evidence of uncontrolled graft-versus-host disease
- Pulmonary: new onset hypoxia
- Known or suspected hypersensitivity to 5'-azacitidine or mannitol
- Evidence of residual disease either by increased blasts count (> 5%) or persistence of previous known cytogenetics abnormalities
- Peripheral blood neutrophil chimerism: less than 95% donor
I. To evaluate whether maintenance treatment post transplant with 5-azacitidine (azacitidine) can reduce the relapse rate over the current standard of care for high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients.
I. To assess overall survival from the time of 5-azacitidine initiation.
II. To confirm the safety and tolerability of low dose 5'-azacitidine by measuring the frequency of transfusions, frequency of bleeding, frequency of serious infections, and use of filgrastim (G-CSF) support.
III. To evaluate graft function and myeloid and T-cell chimerism after administration of low dose 5'-azacitidine.
IV. To evaluate the incidence of acute and chronic graft versus host disease (GvHD) following the initiation of 5-azacitidine.
I. Correlate treatment with low dose 5’-azacitidine with gene specific methylation in the hematopoietic stem cell (HSC) compartment in cluster of differentiation (CD) 34 cells subpopulations.
II. Correlate treatment with low dose 5’-azacitidine with recurrence of cytogenetic abnormalities in the hematopoietic stem cell (HSC) compartment in CD34 cells subpopulations.
III. Correlate treatment with low dose 5’-azacitidine with normalization of myeloid progenitor frequencies known to be altered in MDS.
IV. Correlate treatment with low dose 5’-azacitidine with level of regulatory T cells (CD4+CD25-FoxP30).
Patients receive azacitidine subcutaneously (SC) on days 1-5. Treatment repeats every 28 days for up to 8-10 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 24 months.
Trial Phase Phase II
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
- Primary ID 13-192
- Secondary IDs NCI-2014-00673
- Clinicaltrials.gov ID NCT01995578